Peripheral nerve fibers growing from the spinal cord or dorsal root ganglion are proposed to be under the influence of differentiating target tissues. The differentiative state of the target tissues may be critical in effecting appropriate nerve fiber pathway formaton and subsequent innervation. Both peripheral limb mesenchyme and developing spinal cord, or products of them, may affect the initiation of growth, the elongation and branching of nerve fibers and their orientation. As such, the interactions of these differentiating tissues of the spinal reflex arc may explain the general means by which nerve fibers seek their targets. The results are expected to elucidate the normal control mechanisms of nerve growth during development. This investigation will incorporate studies utilizing an in vitro paradigm to describe the morphogenetic relationships of central nervous system tissues, the sensory ganglia and peripheral mesenchyme and muscle. These types of relationships are suggested to be an extension of epithelial-mesenchymal interactions. A series of tissue culture experiments of various combinations of larval frog spinal cord explants, dorsal root ganglia and differentiating peripheral tissues will be undertaken with a view toward determining the influences of interacting neural and non-neural tissues on neuritic outgrowth. Of particular concern will be an analysis of nerve fiber growth enhancement and orientation, including the determination of crucial stages of development and the specificity of responses.